EP0079810B1 - Nouveaux dérivés de la phényl-4 quinazoline actifs sur le système nerveux central - Google Patents
Nouveaux dérivés de la phényl-4 quinazoline actifs sur le système nerveux central Download PDFInfo
- Publication number
- EP0079810B1 EP0079810B1 EP82401905A EP82401905A EP0079810B1 EP 0079810 B1 EP0079810 B1 EP 0079810B1 EP 82401905 A EP82401905 A EP 82401905A EP 82401905 A EP82401905 A EP 82401905A EP 0079810 B1 EP0079810 B1 EP 0079810B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- group
- phenyl
- quinazoline
- derivatives
- amine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- VEFDQCSIVBIYFQ-UHFFFAOYSA-N 4-phenylquinazoline Chemical class C1=CC=CC=C1C1=NC=NC2=CC=CC=C12 VEFDQCSIVBIYFQ-UHFFFAOYSA-N 0.000 title claims abstract 3
- 210000003169 central nervous system Anatomy 0.000 title claims description 4
- 239000003814 drug Substances 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims abstract 2
- 229910052736 halogen Inorganic materials 0.000 claims abstract 2
- 150000002367 halogens Chemical class 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 5
- 238000009835 boiling Methods 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 150000003017 phosphorus Chemical class 0.000 claims description 3
- CRVSRCOECJCBAJ-UHFFFAOYSA-N 2,6-dichloro-4-phenylquinazoline Chemical compound C12=CC(Cl)=CC=C2N=C(Cl)N=C1C1=CC=CC=C1 CRVSRCOECJCBAJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- DBKIXSRJBMRMMF-UHFFFAOYSA-N 6-chloro-4-phenyl-1h-quinazolin-2-one Chemical class C12=CC(Cl)=CC=C2NC(=O)N=C1C1=CC=CC=C1 DBKIXSRJBMRMMF-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000003556 anti-epileptic effect Effects 0.000 abstract description 2
- 239000001961 anticonvulsive agent Substances 0.000 abstract description 2
- 229960003965 antiepileptics Drugs 0.000 abstract description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 abstract description 2
- 239000003326 hypnotic agent Substances 0.000 abstract description 2
- 230000000147 hypnotic effect Effects 0.000 abstract description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
- 239000003204 tranquilizing agent Substances 0.000 abstract 1
- 230000002936 tranquilizing effect Effects 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229960005152 pentetrazol Drugs 0.000 description 4
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- PDVBMNDBLYNSIS-UHFFFAOYSA-N 6-chloro-4-phenylquinazoline Chemical group C12=CC(Cl)=CC=C2N=CN=C1C1=CC=CC=C1 PDVBMNDBLYNSIS-UHFFFAOYSA-N 0.000 description 2
- 229920004011 Macrolon® Polymers 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- -1 hydroxylamino group Chemical group 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229940082150 encore Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000926 not very toxic Toxicity 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
Definitions
- the present invention relates, as new industrial products, to 6-chloro-4-phenyl-quinazoline derivatives substituted in position 2 by a hydroxyamino group, as well as to their method of preparation and their use as medicaments.
- the compounds (I) provide, with mineral or organic acids, soluble salts. These salts, with pharmaceutically acceptable acids, form an integral part of the invention.
- the compounds (I) can be prepared from suitably substituted 6-chloro-4-phenyl-quinazolone-2 (1) according to the reaction scheme:
- the salts of the compounds (1) are obtained in the usual way by salifying the base when hot with a stoichiometric amount of acid in a suitably chosen solvent so that the salt formed crystallizes on cooling.
- the starting quinazolones 1 are known compounds which can in particular be prepared by the action of potassium cyanate on a 2-amino-5-chloro-benzophenone.
- Chloro-6 (2-chloro-phenyl) -4 (4-hydroxy-piperidinyl-1) -2 quinazoline, hydrochloride (CM 40331).
- the products according to the invention were subjected to pharmacological tests in order to determine their activity on the central nervous system.
- the animals are marked, weighed, placed in pairs in macrolon cages (30 x 19 x 12 cm) and kept in the air-conditioned animal house until the day of the experiment. Food and drink are administered ad libitum. On the day of the experiment, the animals are placed in the laboratory where the experiment is to take place.
- the products to be studied are suspended in gummed water at 5% and administered orally at a dose of 200 mg / kg (expressed as salt) to batches of 10 mice in a volume of 20 ml / kg.
- the witnesses receive the gummed water alone.
- mice are placed in individual containers (10 x 10 x 15 cm). One hour after the administration of pentetrazol the mortality is noted.
- results are expressed as a percentage of animals which have survived, that is to say as a percentage of animals which have been protected from the action of pentetrazol.
- the animals are marked, weighed, placed in pairs in macrolon cages (30 x 19 x 12 cm) and kept in the air-conditioned animal house until the day of the experiment. Food and drink are administered ad libitum. On the day of the experiment, the animals are placed in the laboratory where the experiment is to take place.
- the products to be studied are suspended in gummed water at 5% and administered orally at a dose of 120 mg / kg (expressed as salt) to batches of 10 mice in a volume of 20 ml / kg.
- the witnesses receive the gummed water alone.
- pentobarbital pentobarbital sodium 6%
- pentobarbital sodium 6% pentobarbital sodium 6%
- the products of the invention are not very toxic. All of the products tested are completely non-toxic at a dose of 500 mg / kg.
- the products may be packaged in dosage forms corresponding to the oral route (powders, tablets, capsules %) and the parenteral route (injectable ampoules).
- variable dosage depending on the conditions to be treated and the route of administration will be progressive and will be between 100 and 600 mg per day in adults.
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Luminescent Compositions (AREA)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT82401905T ATE17576T1 (de) | 1981-10-21 | 1982-10-18 | 4-phenyl-quinazolin-derivate wirksam auf das zentralnervensystem. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8119767A FR2514765A1 (fr) | 1981-10-21 | 1981-10-21 | Nouveaux derives de la phenyl-4 quinazoline actifs sur le systeme nerveux central |
| FR8119767 | 1981-10-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0079810A1 EP0079810A1 (fr) | 1983-05-25 |
| EP0079810B1 true EP0079810B1 (fr) | 1986-01-22 |
Family
ID=9263248
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP82401905A Expired EP0079810B1 (fr) | 1981-10-21 | 1982-10-18 | Nouveaux dérivés de la phényl-4 quinazoline actifs sur le système nerveux central |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US4499092A (ko) |
| EP (1) | EP0079810B1 (ko) |
| JP (1) | JPS5888369A (ko) |
| KR (1) | KR880001077B1 (ko) |
| AT (1) | ATE17576T1 (ko) |
| AU (1) | AU551938B2 (ko) |
| CA (1) | CA1236102A (ko) |
| CS (1) | CS229692B2 (ko) |
| DD (1) | DD210040A5 (ko) |
| DE (1) | DE3268699D1 (ko) |
| DK (1) | DK156063C (ko) |
| ES (1) | ES516694A0 (ko) |
| FI (1) | FI73982C (ko) |
| FR (1) | FR2514765A1 (ko) |
| GR (1) | GR76535B (ko) |
| HU (1) | HU187579B (ko) |
| IE (1) | IE53653B1 (ko) |
| IL (1) | IL66960A0 (ko) |
| NO (1) | NO164167C (ko) |
| NZ (1) | NZ202237A (ko) |
| PT (1) | PT75667B (ko) |
| SU (1) | SU1299511A3 (ko) |
| YU (1) | YU43528B (ko) |
| ZA (1) | ZA827516B (ko) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2521144A1 (fr) * | 1982-02-08 | 1983-08-12 | Sanofi Sa | Nouveaux derives de la piperazinyl-2 phenyl-4 quinazoline possedant des proprietes antidepressives, methode de preparation desdits composes et medicaments en contenant |
| WO1994007498A1 (en) * | 1992-10-07 | 1994-04-14 | Sumitomo Pharmaceuticals Company, Limited | Pharmaceutical composition for inhibiting tumor necrosis factor production |
| JPH11209350A (ja) | 1998-01-26 | 1999-08-03 | Eisai Co Ltd | 含窒素複素環誘導体およびその医薬 |
| AU2004236239A1 (en) * | 2003-04-30 | 2004-11-18 | The Institutes For Pharmaceutical Discovery, Llc | Substituted heteroaryls as inhibitors of protein tyrosine phosphatases |
| WO2005042501A1 (en) * | 2003-11-03 | 2005-05-12 | Warner-Lambert Company Llc | Novel norepinephrine reuptake inhibitors for the treatment of central nervous system disorders |
| JP4769866B2 (ja) * | 2005-06-27 | 2011-09-07 | エフ．ホフマン−ラ ロシュ アーゲー | クロロ置換グアニジン |
| US7855194B2 (en) | 2006-03-27 | 2010-12-21 | Hoffmann-La Roche Inc. | Pyrimidine, quinazoline, pteridine and triazine derivatives |
| BRPI0719111A8 (pt) | 2006-11-22 | 2019-01-15 | Sumitomo Chemical Co | agente para inibir a sinalização de citocinina |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA894239A (en) * | 1972-02-29 | Pfizer Inc. | Nitrogen heterocycles | |
| US3305553A (en) * | 1965-10-18 | 1967-02-21 | Parke Davis & Co | 2-aminoquinazoline derivatives |
| US3509141A (en) * | 1966-09-15 | 1970-04-28 | Ciba Geigy Corp | 2-amino-quinazolines |
| GB1347493A (en) * | 1971-02-11 | 1974-02-27 | Aspro Nicholas Ltd | Benzazine derivatives |
| JPS5398997A (en) * | 1977-02-09 | 1978-08-29 | Sumitomo Chem Co Ltd | Fused pyridine derivertives and process for their preparation |
-
1981
- 1981-10-21 FR FR8119767A patent/FR2514765A1/fr active Granted
-
1982
- 1982-09-29 GR GR69402A patent/GR76535B/el unknown
- 1982-10-05 YU YU2233/82A patent/YU43528B/xx unknown
- 1982-10-08 IE IE2447/82A patent/IE53653B1/en not_active IP Right Cessation
- 1982-10-11 IL IL66960A patent/IL66960A0/xx not_active IP Right Cessation
- 1982-10-12 PT PT75667A patent/PT75667B/pt not_active IP Right Cessation
- 1982-10-14 ZA ZA827516A patent/ZA827516B/xx unknown
- 1982-10-18 AT AT82401905T patent/ATE17576T1/de not_active IP Right Cessation
- 1982-10-18 DE DE8282401905T patent/DE3268699D1/de not_active Expired
- 1982-10-18 EP EP82401905A patent/EP0079810B1/fr not_active Expired
- 1982-10-19 US US06/435,230 patent/US4499092A/en not_active Expired - Fee Related
- 1982-10-19 CS CS827411A patent/CS229692B2/cs unknown
- 1982-10-20 KR KR8204715A patent/KR880001077B1/ko active
- 1982-10-20 CA CA000413787A patent/CA1236102A/en not_active Expired
- 1982-10-20 SU SU823502049A patent/SU1299511A3/ru active
- 1982-10-20 HU HU823354A patent/HU187579B/hu not_active IP Right Cessation
- 1982-10-20 DK DK465182A patent/DK156063C/da not_active IP Right Cessation
- 1982-10-20 FI FI823580A patent/FI73982C/fi not_active IP Right Cessation
- 1982-10-20 NO NO823491A patent/NO164167C/no unknown
- 1982-10-20 NZ NZ202237A patent/NZ202237A/en unknown
- 1982-10-20 AU AU89628/82A patent/AU551938B2/en not_active Ceased
- 1982-10-20 DD DD82244148A patent/DD210040A5/de unknown
- 1982-10-20 ES ES516694A patent/ES516694A0/es active Granted
- 1982-10-21 JP JP57183801A patent/JPS5888369A/ja active Pending
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